The Yale SPORE in Skin Cancer program is focused on two skin cancers, basal cell carcinoma (BCC) and melanoma. The goals are to conduct epidemiologic and genetic studies on early onset basal cell carcinoma (Project 1), establish novel high-throughput prognostic and diagnostic tools for melanomas (Projects 2 and 4), and introduce novel targeted therapies to treat melanoma (Projects 2 and 3). The new approaches include genome-wide monitoring of melanoma tumor responses to epigenetic modifiers (Project 2); the use of high-density protein microarrays (ProtoArrays) to interrogate serological responses in sera from melanoma patients (Project 4); and novel epigenetic modifier and immune modulation therapy for melanoma (Projects 2 and 3, respectively). The SPORE includes Administration, Specimen Resource and Bioinformatics/Biostatistics Cores to support the studies of SPORE investigators. Developmental Research and Career Development Award Programs are proposed. The Yale SPORE in Skin Cancer will be an integral part of the Yale Comprehensive Cancer Center (YCCC), Yale New Haven Hospital, and the Dermatology, Pathology and Epidemiology/Public Health Departments that collectively will provide the patient populations, specimens and other resources and support systems needed for the SPORE activities. There is a full commitment from the Dean of Yale School of Medicine and the Director of the YCCC/Chairman of Dermatology to support the SPORE with a plan for cost sharing. The major Translational Results expected are: a) Guidelines for preventive interventions aimed at reducing the incidence of early and total BCC that will diminish the management costs of the most common skin cancer; b) The introduction of new molecular tools for assessing responses to novel epigenetic modifiers; c) The introduction of new ways of assessing melanoma patients employing serological markers; d) The application of new approaches to personalize melanoma chemo- and immuno- therapy; e) The establishment of a composite databases for skin cancers that includes specimens tracking, clinical information, high throughput proteomics and genomics. The database program will be compatible with caBIG and will be available on the web for the benefit of the wider community of investigators and clinicians; f) The creation of new translational bioinformatics tools (predictive statistics and artificial intelligence) required to analyze global and highly complex information derived from different sources and different platforms.